Oligosaccharides which correspond to small fraction of natural bacterial capsular polysaccharides are recognized by antibodies raised against high molecular weight native polysaccharide antigens. The oligosaccharides give promising possibilities as lead vaccine candidates as they are not only immunogenic, but can also function as haptens in their protein conjugates that can elicit specific antibodies in animal models and in humans. Advances in the field of biological research and new generation organic synthetic vaccine technology have provided more effective chemical assembly of the complex oligosaccharide fragments in organic synthetic lab which are generally available on and are purified from the surface of pathogenic bacteria.
The conjugates obtained from natural polysaccharides have been successfully developed as human vaccines. However, their use is associated with problems such as significant variation in size and properties of bacterial polysaccharides, the destruction of vital immuno-dominant features during the chemical conjugation to a carrier protein, display of significant heterogeneity in conjugates and presence of highly toxic components and other host cell impurities that may be difficult to remove. Organic synthesis can provide carbohydrate epitopes in high purity and in relatively large amounts for controlled conjugation to a carrier protein. In such an approach, synthetic saccharides are equipped with an artificial spacer to facilitate selective conjugation to a carrier protein.
The advent of conjugate vaccines against Haemophilus influenzae type b-associated diseases have opened a new era in vaccinology. One of the major milestones in the development of new generation vaccines is the development of efficacious protein conjugates of synthetic fragments of the capsular oligosaccharide of Haemophilus influenzae type b in preventing childhood meningitis and other diseases. The key issues pertaining to the development of synthetic oligosaccharide and their conjugates are manifold such as epitope size, the number of oligosaccharide copies per protein in the conjugate, the possible effect of the spacer on immune response, and the proper choice of the carrier protein combined with the selection of the animal model.
Given the fact that the synthetic oligosaccharide provides the effective lead compounds for the biological research, specifically in the field of vaccine technology, the significant research is going on for the preparation of the synthetic oligosaccharides and their protein conjugates. However, there is no general protocol for the preparation of the oligosaccharide of the biological importance. The chemical synthesis of each lead conjugate molecule is a research project which takes long and systematic experimentation. The total process time documented in the prior art from raw material to the product takes 20-24 hours. The lower yield, less stability and less purity of the conventional oligosaccharide and their protein conjugate are the main issues of concern. Therefore, there is an urgent long felt need to have synthetic oligosaccharide-protein conjugates with higher stability coupled with homogeneity and an efficient synthetic OS-PR conjugation process to obtain such synthetic conjugate vaccines with better yield, stability and purity. The affordability and availability of the synthetic conjugate vaccines is a significant problem which requires a process that enables the availability of synthetic conjugate vaccines in a time-effective and cost-effective manner.